The research program attempts to describe, in molecular terms, the genome and replication of the human hepatitis B virus (HBV), and the role of HBV in the pathogenesis of acute and chronic disease associated with type B hepatitis. This problem will be approached by 1) characterization of the forms of viral DNA, MRNA, and virion intermediates in clinical specimens of infected tissues, 2) analyzing the interaction of HBV with cultured human hepatocytes with the objective of identifying and overcoming the block of HBV replication in tissue culture, and 3) identifying and studying the replication of animal viruses which are structurally similar to HBV.